Because Epstein-Barr virus (EBV) has been associated clinically with some cases of aplastic anemia, we have sought the presence of this virus using immunologic and molecular methods in the bone marrows of patients with pancytopenia and pure red blood cell aplasia. In 6 patients with aplastic anemia and 2 patients with red cell aplasia (one with prolonged aplastic crisis of sickle cell disease, the second an acypical relapse in Diamond-Blackfan syndrome). EBV has been demonstrated by the presence of nuclear antigen (EBNA) with immunofluorescence and of DNA by in situ hybridization and Southern analysis. The pattern of restriction fragments obtained on Southern analysis of DNA from marrow cultures of aplastic anemia patients has been more similar to a non- transforming type of EBV than to the typical transforming EBV of infectious mononucleosis. EBV appears to be capable of infecting an hematopoietic progenitor cell at the BFU-E stage. When normal bone marrow is exposed to EBV or autologous EBV lymphoblastoid cell lines, virus can be demonstrated in the isolated progeny of erythroid colonies by immunofluorescent and molecular methods. EBV is not directly cytotoxic to progenitor cells. However, T lymphocytes that have been exposed to EBV are capable of specifically inhibiting erythroid colony formation by EBV infected bone marrow. These results suggest that hematopoietic suppression associated with EBV may be the result of an immune response with activation of suppressor T lymphocytes. Parallel studies with cytomegalovirus have suggested that CMV is not capable of inhibiting or infecting hematopoietic progenitor cells.